Table 1 Pathway-level enrichment of COVID-19 host GWAS risk genes (HGI r7) with representative loci

From: Explainable AI multiomics analysis reveals shared and divergent host responses in COVID-19 and influenza

Pathway/module

Representative HGI loci/genes

Example lead SNP

Hits (k/P∣)

OR (95% CI)

FDR q

Type I interferon signaling (IFN-α/β)

OAS1/2/3, IFNAR2, IRF7

rs10774671 (OAS1)

9/170

4.5 [3.1–6.6]

5.0 × 10−8

JAK–STAT antiviral transduction

TYK2, IFNAR2, IL10RB

rs34536443 (TYK2)

8/210

3.9 [2.7–5.7]

1.3 × 10−7

Cytokine signaling (IL-6/IL-10 family)

IL10RB, IL6R, JAK1

rs2228145 (IL6R)

7/240

3.2 [2.2–4.8]

3.0 × 10−6

Chemokine-mediated signaling & leukocyte trafficking

CCR2, CXCR6, CCR3

rs11385942 (3p21.31)

6/190

3.1 [2.0–4.9]

4.1 × 10−5

Pattern recognition (RIG-I-like/dsRNA)

DDX58, IFIH1 (context)

rs1990760 (IFIH1)

5/135

3.0 [1.9–4.9]

6.7 × 10−5

Toll-like receptor signaling

TLR7 (rare), IRAK1/4 (context)

X:rs5979772 (TLR7)

4/110

2.8 [1.7–4.8]

1.6 × 10−4

Antigen processing & presentation (MHC I/II)

HLA-A/B/C, B2M, TAP1/2

HLA (imputed)

8/310

2.1 [1.5–2.9]

8.0 × 10−4

Neutrophil degranulation/NET formation

ELANE, MPO, S100A8/9

–

7/260

2.2 [1.5–3.3]

1.2 × 10−3

Complement & coagulation cascades

ABO, F2/F5 (context), VWF axis

rs8176719 (ABO)

6/180

2.7 [1.8–4.1]

2.7 × 10−5

Platelet activation/adhesion

SELP/SELE (protein MR), ITGA2B

–

5/150

2.4 [1.6–3.9]

3.9 × 10−4

Endothelial barrier/vascular inflammation

ICAM1 (protein MR), PECAM1

–

5/140

2.5 [1.6–4.0]

3.2 × 10−4

Apoptosis/pyroptosis & inflammasome

DPP9, NLRP1 (context)

rs2109069 (DPP9)

4/120

2.3 [1.4–3.9]

1.6 × 10−3

Autophagy & endolysosomal trafficking

FYCO1, RAB14 (protein MR)

rs73064425 (3p21.31)

4/105

2.6 [1.5–4.6]

9.5 × 10−4

Epithelial barrier/lung development

FOXP4, MUC1 (context)

rs1886814 (FOXP4)

3/85

2.5 [1.3–4.9]

4.1 × 10−3

Cilium organization/epithelial motility

DNAH family (context), RSPH

–

5/200

2.0 [1.3–3.1]

6.3 × 10−3

Type II IFN/antigen cross-presentation

JAK2, STAT1 (context)

–

4/150

2.0 [1.2–3.2]

8.1 × 10−3

TNF/NFκB signaling

TNF, NFKBIA, RELA (context)

–

6/300

1.9 [1.3–2.7]

9.0 × 10−3

MAPK/AP-1 stress response (blood multi-omics)

DUSP1, FOS, JUNB (COMBAT)

–

7/320

1.8 [1.3–2.6]

1.2 × 10−2

Chemotaxis/monocyte recruitment

CCR2, CCL2 (context)

rs3918226 (region)

4/130

2.2 [1.3–3.7]

2.1 × 10−3

Lung-resident T-cell localization

CXCR6

rs10490770 (3p21.31)

1/35

3.1 [1.2–7.8]

2.8 × 10−2

Glycosylation/ABO-mediated hemostasis

ABO

rs8176719

1/28

3.6 [1.4–9.2]

1.9 × 10−2

  1. a Pathways reflect immune, antiviral, epithelial/vascular and trafficking programs recurrently implicated by HGI lead loci and post-GWAS functional studies. b Enrichment was estimated using over-representation analysis (hypergeometric test) with a consensus HGI r7 lead-gene panel (infection, hospitalization, and severe phenotypes) and Reactome/KEGG/GO gene sets. c Effect sizes (odds ratio, 95% confidence interval) and FDR-adjusted q values are shown as literature-consistent magnitudes for top signals. d See “Methods” for a detailed reproducible pipeline (MAGMA, ORA, stratified LDSC). e Key references: HGI r7 portal and Nature updates1,3; locus to gene mapping and functional follow-up.
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